The initial purpose of this project was to study the natural history of chronic lymphocytic leukemia (CLL), to define clinically important disease parameters and to investigate new therapeutic approaches. Total body irradiation (TBI) alone or with chemotherapy has been shown to yield Type-I response in more than one-third of patients, and this type of response has been correlated with prolonged survival. Commonly employed regimens using alkylating agents and steroids give significantly lower Type I response rates and survival rate. All studies to date have employed historical controls, and have not stratified treatment response with regard to stage of disease. This study has been redirected to examine the therapeutic benefit of TBI and chemotherapy vs. chemotherapy alone in a prospective, randomized, staged group of patients with advanced CLL in whom therapeutic intervention is justified.